Role of Ashwagandha in Cancer

Ashwagandha or Asgandh (Withania somnifera) belongs to the Solanaceae family. It is extensively grown in the Indian subcontinent. As the name indicates, it has a horse's characteristic odor. Ashwagandha contains many bioactive compounds having antioxidant, anti-inflammatory, and immunomodulatory properties. It is used to prevent and treat many diseases, such as arthritis, epilepsy, depression, diabetes, impotence, amnesia, anxiety, cancer, neurodegenerative and cardiovascular diseases. It also has analgesic, rejuvenating, regenerating, and growth-promoting properties.

Ashwagandha is also known as Indian ginseng due to its adaptogen properties. It is commonly used in Indian traditional medicine to promote vigor and vitality, enhance muscle strength, and improve overall health. Several studies have shown the health restorative properties of Ashwagandha by counteracting chronic fatigue, weakness, impotence, sterility, nervous exhaustion, senility, and premature ageing. Studies have shown that Ashwagandha effectively reduces stress and anxiety and increases memory and cognition. The ability of Ashwagandha to influence oxidative stress parameters has also been reported. It has been proved that Ashwagandha is an effective immunomodulatory agent and inhibits myelosuppression. Its immunomodulatory effect is due to a significant increase in cell-mediated immunity.

In the last two decades, Ashwagandha and its active ingredient Withaferin A (WFA) have shown great cytotoxic activity which suggests its potential as an anti-carcinogenic agent in the treatment of several cancers.

Ashwagandha for Breast Cancer

Ashwagandha and its active ingredient Withaferin A (WFA) have been extensively shown to affect all molecular subtypes of breast cancers, including oestrogen-receptor and progesterone-receptor positive or negative cancer, HER2 (human epidermal growth factor receptor 2) negative or positive cancer, and triple-negative (oestrogen-receptor, progesterone-receptor, and HER2 negative) via diverse pathways. Withaferin A can bind to vimentin intermediate filaments causing them to aggregate in the cytoplasm leading to apoptosis in the breast cancer cells. Treatment with the root extract Ashwagandha inhibits mammary cancer metastases and epithelial to mesenchymal transition via vimentin inhibition. These results provided insight into the molecular mechanism of Withaferin A-induced apoptosis in human breast cancer cells. Ashwagandha activates p53 tumor-suppressor protein in tumor cells and causes tumor suppression. Studies show that Ashwagandha extracts selective kill cancer cells by induction of ROS (Reactive Oxygen Species) production and mitochondrial damage and therefore it can be used in treatment of cancer.

Ashwagandha for Colorectal Cancer

Ashwagandha extract is found to have an anti-carcinogenic effect on colorectal tumors through alterations of multiple signaling pathways. The anti-cancer effects of Ashwagandha on the proliferation and migration of colorectal cancer cells have been cited due to the reduced transcriptional activity of STAT3 (signal transducer and activator of transcription 3).

Ashwagandha for Prostate Cancer

Ashwagandha extract has been utilized as a therapeutic agent for prostate cancer, where it acts as a regulator of the G2/M phase transition of the cell cycle. Among different mechanisms involved in prostate cancer genesis and progression, activated protein kinase B/Akt plays an essential role where the inactivation of the tumor suppressor PTEN gene (phosphatase and tensin homologue) causes the activation of Akt and subsequent development of prostate tumors. Oral administration of Ashwagandha extract inhibited the activation of the Akt enzyme. Treatment with Ashwagandha extract leads to apoptosis in prostate cancer cells by Androgen receptor function suppression or blocking androgen signaling.

Ashwagandha for Lung Cancer

Ashwagandha extract is effective in non-small cell lung cancer (NSCLC). Ashwagandha induces apoptotic cell death in epidermal growth factor receptor-positive and mutant NSCLC cell lines. Ashwagandha is effective for targeting KRAS mutant NSCLC cell lines. Ashwagandha was shown to have an anti-proliferative and pro-apoptotic activity on lung cancer via suppression of the PI3/Akt pathway. It inhibits invasion and metastasis of lung cancer by inhibiting epithelial to mesenchymal transition (EMT) and reducing cell adhesion.

Ashwagandha for Ovarian Cancer

Amongst other cancers, Ashwagandha has also shown tremendous efficacy in ovarian cancer treatment, particularly in combination therapy. A combination of Ashwagandha and cisplatin has proven an effective treatment of refractory ovarian cancer.

Benefits of Ashwagandha in other Cancers

Apart from the major cancers described above, Ashwagandha also shows potent anti-cancer properties in several other cancers, such as gastric cancer, papillary and anaplastic thyroid cancers, cervical cancers, melanomas, renal cell carcinoma, and promyelocytic leukaemia.

In gastric cancer, Ashwagandha inhibits the proliferation of human gastric adenocarcinoma by inducing G2/M cell cycle arrest and apoptosis. In addition to killing cancer cells, Ashwagandha targets cancer stem cells and metastatic cancer cells.

Ashwagandha restores the inactivation of the tumor suppressor p53 protein, thus downregulating human papillomavirus (HPV) expressing E6/E7 oncogenes both in vitro and in vivo.

In the case of melanoma, Ashwagandha induces apoptotic cell death with the involvement of the mitochondrial pathway.

When treated with Ashwagandha, endoplasmic reticulum stress was the driving force in human renal carcinoma cells. Ashwagandha induced apoptotic cell death in renal carcinoma cell lines and induction of ER (endoplasmic reticulum) stress markers.

Ashwagandha is beneficial in hepatocellular carcinoma cells due to its antioxidant and pro-apoptotic activity. Its antioxidant properties also protect against radiation-induced hepatotoxicity.

Recently, researchers investigated the action and mechanism of Ashwagandha on cancer cells. Maintenance of telomere length by activation of telomerase or ALT (Alternative mechanism of Lengthening of Telomeres) led to overcome replicative mortality of cancer cells, and Ashwagandha was found to have more potent cytotoxic effects on ALT cells by telomere dysfunction, DNA damage, upregulation, and inhibition of ALT-associated promyelocytic leukemia nuclear bodies in these cells.

Role of Ashwagandha in Chemotherapy-Induced Toxicities

Traditional chemotherapies have many adverse effects, including those affecting functions of several organs such as the heart, liver, kidney, etc. Pre-treatment with Ashwagandha induces apoptosis in cancer cells and inhibition of oxidative stress. Ashwagandha decreases acute pancreatitis caused by oxidative stress and inflammation. Lastly, Ashwagandha has been found to induce antifibrotic activity in scleroderma by suppressing pro-inflammatory fibrosis. Studies done on 100 breast cancer patients receiving chemotherapies showed the potential of Ashwagandha mediated decrease of treatment-related fatigue and improved quality of life.

Conclusion

Numerous studies have shown the anti-cancer effect of Ashwagandha or its major component, WFA, in various cancers. Ashwagandha can be used as an adjunct therapy that can reduce the adverse effects of radio and chemotherapy due to its anti-inflammatory and antioxidant properties. Ashwagandha can also be combined with other conventional treatments such as chemotherapies to synergize and potentiate the effects of chemotherapy due to its ability to aid in chemosensitization. All evidence to date indicates the potential of Ashwagandha in cancer management.