Best phytochemicals for fighting cancer

Phytochemicals tested for anti-cancer efficacy in vitro and in vivo

Breast cancer cell line

Naturally occurring compounds, that may lead to the development of a new drug, have been sources for novel anti-cancer therapy for a long time. In fact, approximately 50% of all approved anti-cancer drugs from 1940 to 2014 originated from natural products. In particular, of the 175 small molecules approved between 1940s to the end of 2014, 49% of them were actually natural products or originated from natural products. 

In general, the naturally occurring compounds from plants known as phytochemicals have specific mechanisms of action such as increasing anti-oxidant status, carcinogen inactivation, inhibiting proliferation, induction of cell cycle arrest and apoptosis; and regulation of the immune system.

This article summarises the phytochemicals which have been evaluated at a preclinical level (Source: Review“Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice” by Amit S. Choudhari, Pallavi C. Mandave, Manasi Deshpande, Prabhakar Ranjekar and Om Prakash): 

6-Shogaol is a minor, bioactive component isolated from ginger (Zingiber officinale Roscoe)

In a mice model of non-small cell lung cancer, 6-shogaol significantly inhibited the growth of lung cancer cells which was associated with decreased cell proliferation and increased apoptosis. At in vitro level 6-shogaol suppressed Akt signalling (a signal transduction pathway that promotes survival and growth in response to extracellular signals). In another mice model of prostate cancer, intraperitoneal administration of 6-shogaol reduced tumour weight.

Shogaols are more concentrated in dried ginger, with 6-shogaol being its main source of anti-oxidants. So, like zingerone (major flavour component of ginger), the 6-shogaol is produced when ginger is dried or cooked.

Gingerol is a major phenolic compound present in the rhizomes of ginger (Z. officinale Roscoe)

In a mouse model of spontaneous breast cancer metastasis, gingerol treatment induced apoptosis and inhibited tumour growth, as well as metastasis to multiple organs such as lung, bone and brain. Likewise, in another model gingerol inhibited lung-metastatic human breast cancer cell proliferation and invasion. 

Gingerols are more abundant in raw ginger and activate the spice receptors on the tongue. Molecularly, gingerol is a relative of capsaicin and piperine, though they act on different bioactive pathways.

For more source:"Fighting breast cancer with natural compounds backed by science".

Allicin, one of the main organic allyl sulfur components in garlic (Allium sativum, Amaryllidaceae)

In a mice model of cholangiocarcinoma (a type of cancer that forms in the slender tubes, bile ducts, that carry the digestive fluid bile), allicin significantly suppressed the growth of human liver bile duct carcinoma (HuCCT-1). Then, the in vitro molecular study showed that allicin decreased migration, invasion and epithelial-mesenchymal transition of HuCCT-1 cells. Other in vitro studies, showed that allicin also significantly inhibited adhesion, invasion and migration of lung adenocarcinoma cells.

Allicin is the oily, slightly yellow liquid that gives garlic its distinctive odour. 

Alpinumisoflavone (AIF) is a pyranoisoflavone found in the traditional Chinese herb Derris eriocarpa (Leguminosae)

In a mice xenograft model with human clear cell renal cell carcinoma (ccRCC), AIF suppressed growth and metastasis of human ccRCC cells, and the inhibitory effect was due to increased expression of miR-101 (a tumour suppressor for renal cell carcinoma). In addition, AIF was reported to increase radiosensitivity in esophageal squamous cell carcinoma.

For more source:"Fighting renal cell carcinoma with natural compounds backed by science".

Andrographolide is a bicyclic diterpenoid lactone isolated from Andrographis paniculata (Acanthaceae)

Andrographolide was found to inhibit breast cancer growth by blocking tumour adaptation to hypoxic conditions, due to inhibition of hypoxia-inducible factor HIF-1α activity and its upstream PI3k/AKT/mTOR pathway. HIF-1α is a master regulator of the transcriptional response to hypoxia, a common feature of most tumours. Tumour-hypoxia leads to advanced but dysfunctional vascularisation and acquisition of epithelial-to-mesenchymal transition phenotype resulting in cell mobility and metastasis. Hypoxia also alters cancer cell metabolism and contributes to therapy resistance by inducing cell quiescence. 

Andrographolide is an extremely bitter substance!

Apigenin (APG), is a naturally occurring flavonoid present in fruits and vegetables with diverse anti-cancer properties 

In an athymic mouse xenograft model with human chondrosarcoma cells, APG suppressed tumour growth which was associated with decrease in Ki67 expression (a proliferation marker) and induction of apoptosis. In another study, APG targeted a peptidase enzyme to reduce the growth and metastasis of non-small-cell lung carcinoma xenografts. 

Apigenin, is a yellow crystalline solid that has been used to dye wool, and is found in many fruits and vegetables, but parsley, celery, celery root and chamomile tea are the most common sources. Dried parsley can contain about 45 mg/gr and dried chamomile flower about 3-5 mg/gr apigenin. The apigenin content of fresh parsley is reportedly 215.5 mg/100 gr, which is much higher than the green celery hearts providing 19.1 mg/100 gr.

Baicalein and baicalin are the naturally occurring flavonoids and active components of Scutellaria baicalensis (Lamiaceae)

In a mouse xenograft model with human colon cancer cells, baicalein and baicalin inhibited tumour growth and induced apoptosis. In a similar model of colon cancer, intraperitoneal administration of baicalin also inhibited tumour growth. Furthermore, in combination with docetaxel (chemotherapy drug), baicalein additively inhibited the tumour growth by increasing apoptosis and decreasing tumour angiogenesis.

Baicalein, is the aglycone of baicalin, and is also found in Oroxylum indicum (Indian trumpetflower) and thyme. Baicalein is one of the active ingredients of Sho-Saiko-To, which is a Chinese classic herbal formula, and listed in Japan as Kampo medicine. 

Breast cancer cell line

Curcumin (phytopolylphenol) is a phytochemical from Curcuma longa (Zingiberaceae)

Studies in mice indicated that curcumin inhibited the growth of melanoma cells when subcutaneously injected in mice, through diverse mechanisms including cell cycle arrest, autophagy and downregulation of the PI3K/AKT/mTOR pathway which is a critical intracellular signalling pathway associated with cell survival and death.

For more source: "Curcumin anti-cancer properties and therapeutic activity".

Decursin and decursinol are coumarins purified from the dried roots of Angelica gigas Nakai

In a mice xenograft model with human prostate cancer over-expressing the wild type androgen receptors, decursinol treatment decreased tumour growth and lung metastasis. Decursin is rapidly and extensively converted to decursinol in rodents and humans. 

Dicumarol (DIC) is the natural anti-coagulant derived from coumarin, by bacterial action in spoiled sweet clover hay (Melilotus officinalis, Fabaceae)

In a mouse xenograft model, DIC significantly suppressed the growth of ovarian carcinoma cells and notably DIC was found safe toward ovarian tissues and developing oocytes; implicating an importance of DIC as a potential anti-cancer agent when female fertility preservation is a concern.

Dicoumarol or dicumarol is a naturally occurring anti-coagulant drug that depletes stores of vitamin K (similar to warfarin). 

Epigallocatechin (EGCG), a major catechin found in green tea 

EGCG effectively delayed the tumour incidence and reduced tumour burden by inducing apoptosis and inhibiting proliferation of human breast cancer cells in mouse model. In another study, EGCG suppressed the oxidative stress-derived DNA damage marker levels in mouse lung DNA to inhibit induced lung tumourigenesis.

For more source: "Green tea extract EGCG and cancer chemoprevention”.

Emodin is an anthraquinone derivative from the root and rhizome of Rheum palmatum L. (Polygonaceae)

In mice models bearing breast tumours, emodin suppressed tumour growth by inhibiting macrophage infiltration, accompanied by increased T-cell activation and reduced tumour angiogenesis. In another mice model, emodin inhibited the growth of human lung epithelial cancer cells by inducing apoptosis. Finally, in a mice xenograft model with human hepatocellular cancer cells, emodin suppressed tumour growth and induced apoptosis.

Emodin it is specifically isolated from Rheum Palmatum L, commonly called Chinese rhubarb, ornamental rhubarb, Turkey rhubarb or East Indian rhubarb. 

Genistein is a naturally occurring isoflavone present in soy beans with estrogen-like properties

In athymic mouse xenograft model with human leukemia, intraperitoneal injection of genistein for 28 days significantly reduced the tumour weight without affecting the body weight. At in vitro level, genistein induced cell cycle phase arrest and apoptosis of human leukemia cells. Moreover, genistein treatment decreased the number of total aberrant crypts in a induced rat colon cancer mice model. 

Isoflavone genistein (described as an angiogenesis inhibitor and a phytoestrogen) is found in a number of plants including lupin, fava beans, soybeans, kudzu and psoralea being the primary food source. 

Breast cancer cell line

Glycyrrhizin (GA) is the major bioactive component found in licorice roots of a small leguminous shrub, Glycyrrhiza glabra L

In athymic mice xenograft model with human lung adenocarcinoma cells stably transfected with thromboxane receptor (that stimulates activation of new platelets as well as increases platelet aggregation), GA treatment reduced thromboxane synthase and proliferation via suppressing thromboxane pathway. And more recent findings have showed that GA treatment inhibited the growth of non-small cell lung cancer cells in patient-derived xenograft mice.

Glycyrrhizin is the chief sweet-tasting constituent of liquorice root and structurally it is a saponin used as an emulsifier and gel-forming agent in foodstuffs and cosmetics. 

Licochalcone A (LicA) is a phenol chalconoid isolated from the roots of Glycyrrhiza species

In an athymic mouse model, LicA inhibited the human cervical cancer growth and induced apoptosis. In a similar model with subcutaneous xenograft with human glioma cells, LicA induced cell cycle arrest. Most recently, LicA was shown to suppress hexokinase 2-mediated tumour glycolysis in gastric cancer.

Hispidulin is a phenolic flavonoid compound found in different plant materials such as Saussurea involucrata Kar (Asteraceae)

Intraperitoneal administration of hispidulin inhibited human clear cell renal cell carcinoma growth and lung metastasis in athymic mouse model by modulating ceramide-S1P balance (ceramides favour anti-proliferative and cell death pathways such as senescence and apoptosis). Similarly, in another study hispidulin effectively suppressed human hepatocellular carcinoma cell xenograft tumour growth and lung metastasis.

Hispidulin is a naturally occurring flavone with potential anti-epileptic activity in rats and gerbils, found in plants including Grindelia argentina, Arrabidaea chica, Saussurea involucrate, Crossostephium chinense, Artemisia and Salvia.

Nimbolide is a triterpene derived from the leaves and flowers of the neem tree (Azadirachta indica)

In an athymic mouse model, nimbolide inhibited the pancreatic cancer cell growth and metastasis by inducing apoptosis. The in vitro molecular mechanism studies showed that nimbolide increased ROS generation, inhibited proliferation and metastasis via mitochondrial-mediated apoptotic cell death. Recent in vitro study suggested epigenetic role of nimbolide in regulating autophagy and apoptosis in human breast cancer cells.

Physapubescin B is a steroidal substance isolated from Physalis pubescens L. (Solanaceae)

In mouse models with prostate cancer xenografts, physapubescin B decreased tumour growth and increased the apoptotic cell population within the tumour tissue. Furthermore, in renal cell carcinoma cells physapubescin treatment decreased the protein expression of vimentin and inhibited in vivo angiogenesis.

For more source:"Herbs with Anti-angiogenic Activity to Treat Cancer”

Pterostilbene is a naturally occurring derivative of resveratrol originated from grape (Vitis vinifera, Vitaceae) 

In an athymic mouse esophageal cancer model, pterostilbene significantly inhibited tumour growth, cell adhesion, migration and intracellular glutathione levels while increased the apoptotic index. Similarly, in a athymic mouse model of diffuse large B-cell lymphoma, pterostibene markedly inhibited tumour growth, leading to S-phase arrest in the cell cycle. More importantly, it was demonstrated that pterostilbene with megestrol acetate (an hormonal therapy drug used to treat breast and womb cancer that has spread to other parts of the body) significantly reduced tumour growth in an endometrial cancer xenograft mouse model as compared to pterostilbene or megestrol acetate alone. At in vitro level, the above combination suppressed estrogen receptor expression.

Pterostilbene is a stilbenoid chemically related to resveratrol and in plants has a defensive anti-microbial role.

Resveratrol is a polyphenolic phytoalexin (stilbenoid)

Resveratrol significantly reduced tumour growth and metastasis to the lung in mice bearing highly metastatic Lewis lung carcinoma. The results suggested that the anti-tumour and anti-metastatic activities of resveratrol could result from the inhibition of DNA synthesis, inhibition of neo-vascularisation and angiogenesis. In a mammary cancer model, resveratrol reduced the incidence and multiplicity of tumours, concurrently extending the latency period. 

Resveratrol is produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sources of resveratrol in food include the skin of grapes, blueberries, raspberries, mulberries and peanuts.

HS-1793 is a synthetic analogue of resveratrol with improved photosensitivity and stability profile

In a mouse model of breast cancer, HS-1793 significantly suppressed the growth of human breast cancer cells. Moreover, HS-1793 treatment down-regulated expression of key components of angiogenesis. Apart from its growth inhibitory and anti-angiogenesis effects, HS-1793 enhanced ionising radiation-induced apoptosis and inhibited hypoxia-induced cancer stem cell properties in hypoxic mouse breast cancer cells.

Sulforaphane (SFN) is a compound within the isothiocyanate group of organosulfur compounds 

SFN exerts its anti-cancer effects via induction of apoptosis, inhibition of cell cycle progression, inhibition of angiogenesis and by increasing anti-cancer activity of other anti-proliferative agents including paclitexal. Addition of SFN and paclitexal to Barrett esophageal adenocarcinoma cells significantly increased apoptotic cell death compared to SFN or paclitexal alone. 

Sulforaphane is a natural plant compound found in many cruciferous vegetables like broccoli, cabbage, cauliflower and kale.

Thymol is a transient receptor potential ankyrin subtype 1 channel agonist found in thyme (Thymus vulgaris) and oregano (Origanum vulgare) 

In oral squamous cell carcinoma derived mouse xenografts, intra-tumour injection of thymol reduced the tumour volume with decreasing cell proliferation and inducing apoptosis. The in vitro molecular mechanism studies showed that thymol induced apoptosis.

Thymoquinone (TQ) is the active constituent of black cumin (Nigella sativa, Ranunculaceae) seed oil 

In a athymic mice model, TQ decreased tumour weight and size by inducing apoptosis in human gastric cancer cells. Recent preclinical studies suggested the potential of TQ in adjuvant therapy with other chemotherapeutic agents. In a study in mice transplanted with epithelia breast cancer cell line, TQ in combination with melatonin significantly decreased the tumour size, induced tumour cell death, decreased VEGF expression and activated anti-cancer immune response.

Ursolic acid (UA) is a natural terpene compound found in a variety of plants

In mouse model of colorectal cancer cells (CRC), UA was shown to enhance the therapeutic effects of chemotherapy drug oxaliplatin, by inhibiting the tumour and increasing the survival rate. The in vitro mechanistic study suggested that the combined treatment of CRC cells significantly inhibited cell proliferation, increased apoptosis and significantly inhibited expression of drug resistant genes. 

Withaferin A (WA) is a steroidal lactone present in Withania somnifera (Solanaceae) 

In a mouse model of colorectal cells (CRC), oral administration of WA inhibited the tumour growth of human colorectal carcinoma cells and the micro-vessel formation. In another study, intraperitoneal administration of WA inhibited CRC growth. Similarly, in another study, oral administration of WA effectively inhibited xenografts and induced-hepatocellular carcinoma cells. 

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Until next time,