The Anticancer Effects and Side Effects of Camptotheca (Xi Shu)

Xi Shu (Camptotheca acuminata) is a deciduous tree of the genus Camptotheca in the Nyssaceae family, mainly distributed in southwest China and in Jiangsu, Zhejiang, Fujian, Jiangxi, Hubei, Hunan, Guangdong, Guangxi, and Taiwan. Its fruit, root, and root bark can all be used medicinally. The fruit, root, and root bark all contain alkaloids such as camptothecin and 10-hydroxycamptothecin. Camptothecin-like substances isolated from Camptotheca can selectively inhibit DNA topoisomerase I, showing antitumor activity; camptothecins have been developed into chemotherapy drugs.

Among the folk, Xi Shu fruit, leaves, bark, root, and root bark are all used as a specific treatment for furuncles and psoriasis. A decoction of various parts for external washing, or an ointment made from its extract with Vaseline for external application, can treat psoriasis, chronic eczema, dermatitis, and skin warts. Xi Shu also has antiviral activity against herpes virus. There are reports that the effective rate of Xi Shu for psoriasis can reach as high as 76.62%, although during treatment a few patients develop local irritation reactions such as intense itching, burning pain, or flushing; in rare cases the skin erodes, but this resolves on its own after stopping the drug.

Xi Shu is not recorded in ancient TCM literature; it appears only in contemporary regional herbal records and in the National Compilation of Chinese Herbal Medicine. TCM holds that Xi Shu is bitter and pungent, cold in nature, and toxic, entering the Spleen, Stomach, and Liver meridians; it clears heat and resolves toxin, and reduces swelling and disperses nodules. Xi Shu has broad-spectrum anticancer activity and can treat esophageal cancer, cardia cancer, gastric cancer, intestinal cancer, liver cancer, lung cancer, leukemia, nasopharyngeal cancer, bladder cancer, breast cancer, cervical cancer, ovarian cancer, prostate cancer, and malignant melanoma, among other tumors.

The camptothecin and 10-hydroxycamptothecin in Xi Shu are its main anticancer components, but both are quite toxic. In mice, the LD50 of a single intraperitoneal injection of camptothecin is 68.4–83.6 mg/kg; the LD50 of intravenous sodium camptothecinate is 57.3 mg/kg; by gavage it is 153.2 mg/kg; intraperitoneally 8.81 mg/kg. The LD50 of intraperitoneal 10-hydroxycamptothecin in mice is 104 mg/kg.

The adverse reactions of camptothecin and 10-hydroxycamptothecin mainly involve the gastrointestinal tract and hematopoietic system. Most patients experience nausea, vomiting, and bone marrow suppression (decreased white blood cells, neutrophils, lymphocytes, and platelets), which gradually recover after stopping the drug. Camptothecin and 10-hydroxycamptothecin also have adverse effects on the liver, kidneys, and gallbladder of experimental animals. Camptothecin and 10-hydroxycamptothecin can increase patients' appetite and body weight.

In modern clinical practice, the active components camptothecin and 10-hydroxycamptothecin, extracted from Xi Shu, are mainly given by injection during chemotherapy. But in folk practice, Xi Shu fruit and bark can be decocted or ground to powder for oral use. The usual oral dose of Xi Shu root bark in decoction is 10–15 g, and of Xi Shu fruit 3–10 g. The oral dose should not be too large, as overdose easily causes poisoning, though some doctors use up to 50–100 g of Xi Shu fruit.

Xi Shu has shown good efficacy in treating metastatic liver cancer. Clinical reports show that in combined regimens, adding 10–20 mg of hydroxycamptothecin to the first-line chemotherapy regimen for the primary tumor can markedly improve the chemotherapy response rate, with the most prominent effects on liver metastases from proliferative small-cell lung cancer, poorly differentiated pulmonary adenocarcinoma, and breast cancer.

Another report describes using camptothecin for interventional embolization in 18 patients with inoperable and advanced bladder cancer: tumors in 17 patients showed varying degrees of necrosis and shrinkage, and hematuria disappeared in all of them, with only one patient showing no response. In addition, hydroxycamptothecin combined with radiotherapy for nasopharyngeal carcinoma has also achieved marked efficacy.

Adding Xi Shu fruit or bark to TCM compound formulas can improve the success rate of anticancer treatment. TCM compound formulas can address multiple aspects simultaneously; when using Xi Shu fruit or bark, it can be combined with herbs that support the root and bolster the constitution, protect the liver and gallbladder, and protect the stomach and kidneys. This is safer than using camptothecin or 10-hydroxycamptothecin alone, and can also enhance their anticancer efficacy.