Herbal Ashwagandha Kills Osteosarcoma Cells in Vitro

Osteosarcoma is a type of bone cancer found mostly in teenagers and people over age 60.

Most cases of osteosarcoma are associated with genetic syndromes. In other words, Osteosarcoma is associated with a genetic preposition inherited from the parent.

According to the statistic from the American Cancer Society, each year, approximately 800 to 900 new cases of osteosarcoma are diagnosed in the United States with half of these are in children and teens.

The exact causes of osteosarcoma are unidentified. However, epidemiologically, besides gene expression, an unhealthy lifestyle such as body weight, physical activity, diet, and tobacco, gender, age, height, ethnicity and exposure to bone radiation are also some prevalent factors found in patients with the disease.

Dr. Jeff W. Martin, the lead scientist at the Hospital for Sick Children and Queen's University wrote, "The etiology of this often aggressive cancer is currently unknown because complicated structural and numeric genomic rearrangements in cancer cells preclude the understanding of tumor development.",

And, " few consistent genetic changes that may indicate effective molecular therapeutic targets have been reported. However, high-resolution techniques continue to improve knowledge of distinct areas of the genome that are more commonly associated with osteosarcomas".

The overall 5-year survival rate for children and teens with osteosarcoma is 70%. If cancer has spread to the lung, the 5-year survival rate is only 40% compared to localized cancer between 60% to 80%.

Conventionally, most cases of osteosarcoma are o treated with a combination of surgery, chemotherapy and radiation therapy.

In patients with high-grade tumors, before surgery, neo-adjuvant therapy may be necessary to shrink the tumor.

Ashwagandha (WA)also is known as Withania somnifera is a nightshade plant in the genus of Withania, belonging to the family Solanaceae, native to the dry parts of India, North Africa, Middle East, and the Mediterranean. The herbal medicine has been considered as Indian ginseng and used in Ayurvedic medicine over 3000 years to treat tumors and tubercular glands, carbuncles, memory loss, and ulcers and considered as anti-stress, cognition-facilitating, anti-inflammatory, and anti-aging herbal medicine.

On finding a potent compound for the treatment of cancers, researchers examined evaluated the safety and pharmacokinetics of WA.

In Vitro, Withaferin-A (WF-A), a major bioactive compound found in WA exhibited strong antiproliferative activity against several osteosarcoma cell lines, with IC50 ranging from 0.32 to 7.6 μM. The lowest IC50 (0.32 μM).

At the lowest IC50 (0.32 μM), WF-A showed a significant effect on the inhibition of U2OS cell line, compared to other cell lines.

Most importantly, WF-A induced ROS cytotoxicity against the tested cell lines in a dose-dependent manner and activation of cell death protein in osteosarcoma cells.


In the safety analysis, if the phase I dose-escalation study, using the classical 3 + 3 design (C33D) is comprised of 72, 108, 144 and 216 mg of WA administered in two to four divided doses per day in selected patients, including 3 patients enrolled in each cohort with the last patient who was observed for at least 30 days for any dose-limiting toxicity before progressing to a higher cohort, researchers found that the formulation was generally well tolerated with no grade 3 or grade 4 adverse events were observed, however, the formulation at the tested doses caused 11 adverse events of grade 1 or grade 2 severity.

Mose common symptoms are fatigue, fever, edema, and diarrhea. No levels of WA circulation. were found in the blood plasma. The low oral bioavailability of WA was also observed during the experimental period.
Based on the findings, researchers wrote, "The formulation was well tolerated. However, WA appears to have low oral bioavailability. Further studies with improved formulations are warranted".


Taken altogether, Ashwagandha is safe and may be considered a functional herb for the prevention and an adjunct therapy combined with the primary medicine for the treatment of osteosarcomas, pending to the result of larger sample size and multicenter study

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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

Sources
(1) Safety and Pharmacokinetics of Withaferin-A in advanced stage high grade Osteosarcoma: A phase I trial by Pires N1, Gota V1, Gulia A2, Hingorani L3, Agarwal M2, Puri A. (PubMed)
(2) Withaferin-A Induces Apoptosis in Osteosarcoma U2OS Cell Line via Generation of ROS and Disruption of Mitochondrial Membrane Potential by Zhang HL1,2, Zhang H. (PubMed)
(3) The Genetics of Osteosarcoma by Jeff W. Martin,1 Jeremy A. Squire,2 and Maria Zielenska. (Hindawi)