Common Herbal Product Used in Cancer Prevention and Treatment

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1 Common Herbal Product Used in Cancer Prevention and Treatment Dr. Pran Kishore Deb Assistant Professor Pharmaceutical Medicinal Chemistry Faculty of Pharmacy, Philadelphia University-Jordan

2 Campetothecine It is obtained from the Chinese tree Camptotheca acuminata, and family Nyssaceae. This alkaloid showed broad spectrum activity as anticancer but its toxicity is too high. The natural 10-hydroxy camptothecin is more active and is used in China for neck and head cancer. The synthetic analogues are 9-aminocamptothecin. Particularly, water-soluble derivatives topotecan, irinotecan showed good for the treatment of ovarian cancer and colorectal cancer, while belotecan (camtobell available in USA) is available for small cell lung cancer and ovarian cancer. Irinotecan inhibits the action of topoisomerase I by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death. Side effect of irinotecan: diarrhea, anemia, hair loss, abdominal cramps, vomiting and nausea (common almost to all chemotherapy). 2

3 Irinotecan Campetothecine Topotecan Camptotheca acuminata 3

Podophyllum Podophyllum resin is obtained from rhizomes or roots of Podophyllum peltatum (American podophyllum) or Podophyllum emodi (Indian podophyllum). Family: Berberidaceae.

4 Podophyllum Podophyllum resin is obtained from rhizomes or roots of Podophyllum peltatum (American podophyllum) or Podophyllum emodi (Indian podophyllum). Family: Berberidaceae. It is known as May apple. Constituents: It contains 3.5-6% of resin. The active principle is the lignans, these include podophyllotoxin 20%, -peltatin 10%, and -Peltatin 5%. Etoposide is a lignan derivative obtained semi-synthetically from podophylotoxin and is used for treatment of small-cell lung cancer, testicular cancer as well as lymphomas and leukemias. Etoposide cause inhibition of topoisomerase II resulting in strand breakage leading to apoptosis. Teniposide (synthetic derivative of podophyllotoxin) is also used for the treatment of brain cancer. 4

5 Podophyllotoxin Etoposide Teniposide

Vinca Alkaloids: Vinicristine and vinblastine These are obtained from Catharanthus roseus (Vinca rosea) which is a Madagascar plant (Madagascar periwinkle). Now, it is widely cultivated.

6 Vinca Alkaloids: Vinicristine and vinblastine These are obtained from Catharanthus roseus (Vinca rosea) which is a Madagascar plant (Madagascar periwinkle). Now, it is widely cultivated. The cellular mechanism of action of vinca alkaloids is the prevention of microtubule assembly, causing cells to arrest in the late G2 phase by preventing formation of mitotic filaments for nuclear and cell division. H NH + N H H 3 C H + N H S - - H 3 C N H R Vincristine R = CH Vinblastine R =

assembly/polymerisation of tubulin dimers into microtubules They act

7 Vinka alkaloids (Vinblastine, vincristine) Mechanism of Action: These drugs block the formation of mitotic spindle by preventing the assembly/polymerisation of tubulin dimers into microtubules They act primarily on the M phase of cancer cell cycle Resistance is due to d efflux of drugs from tumor cells 7

8 Vinka alkaloids

Vincristine sulfate (ncovin ) Uses: leukemias, lymphomas, sarcomas, and some carcinomas Vinblastine sulfate (Velban ) Uses: Vinblastine, the more active compound, has had much wide

9 Vincristine sulfate (ncovin ) Uses: leukemias, lymphomas, sarcomas, and some carcinomas Vinblastine sulfate (Velban ) Uses: Vinblastine, the more active compound, has had much wide clinical application, including solid tumors, especially in combination with drugs such as cisplatin and BLM (bleomycin) testicular tumor advanced Hodgkin s disease breast carcinoma

Anti-Cancer Plant Alkaloids Paclitaxel (Taxol) and Docetaxel Paclitaxel and the semisynthetic analogue Docetaxel represent the taxane family of drugs that inhibit

The semisynthetic route involves docetaxel as an intermediate. The term Taxoids is used generally for paclitaxel and its derivatives.

10 Anti-Cancer Plant Alkaloids Paclitaxel (Taxol) and Docetaxel Paclitaxel and the semisynthetic analogue Docetaxel represent the taxane family of drugs that inhibit tubulin depolymerisation. Paclitaxel was isolated from the bark of Yew trees Taxus brevifola in A full synthesis was achieved in The semisynthetic route involves docetaxel as an intermediate. The term Taxoids is used generally for paclitaxel and its derivatives. MA: The taxoids binds to β-subunit of tubulin and accelerates polymerisation as well as stabilises the resultant microtubules, which means that depolymerisation is inhibited. As a result, the cell division cycle is halted.

11 Vinka alkaloids Paclitaxel (Taxol) Accelerate (Direct) Indirect Stabilise

12 Mechanism of Action: Paclitaxel & Docetaxel 12

13 Paclitaxel (Taxol) Uses Leukemias, sarcomas, Lung cancer varian and breast carcinoma HN H H 3 C H 3 C H H Side effects: hair loss, muscle and joint pains, and diarrhea Docetaxel Uses Lung cancer varian and breast carcinoma

14 Thank You

Common Herbal Product Used in Cancer Prevention and Treatment

Common Herbal Product Used in Cancer Prevention and Treatment Dr. Pran Kishore Deb and Dr Balakumar Chandrasekaran Assistant Professor Pharmaceutical Medicinal Chemistry Faculty of Pharmacy, Philadelphia