The Anticancer and Anti-Leukemia Effects of Xiong Huang (Realgar)

The Chinese medicine Xiong Huang is a sulfide mineral of the realgar group, mainly containing arsenic disulfide (As2S2) with a small amount of impurities, mainly produced in Cili and Shimen (Hunan), and Langdai and Sinan (Guizhou). Realgar is a typical mineral of low-temperature hydrothermal and volcanic hydrothermal deposits; it occurs in close intergrowth with Orpiment (Cihuang), whose component is arsenic trisulfide (As2S3). Orpiment is also used medicinally, with effects similar to realgar. In ancient times, besides medicinal use, realgar and orpiment were also used as pigments for writing or painting. The idiom "xin kou ci huang" (literally "carelessly using orpiment") originally meant speaking without credibility, like writing a wrong character and casually erasing it with orpiment.

Both realgar and orpiment, when heated, can be converted into arsenic trioxide (i.e., arsenic), hence the ancient saying "realgar passed through fire is as poisonous as arsenic." Natural realgar contains a small amount of arsenic, so before medicinal use it must undergo a special processing procedure called "water grinding" (shuifei): realgar is ground and suspended in water; the arsenic and other impurities dissolve in water, while realgar is insoluble and floats on the surface; the floating material is carefully skimmed off and dried at low temperature to obtain higher-priority water-ground realgar. Water-ground realgar is less toxic than natural realgar and safer for medicinal use.

Realgar is not used in decoction but in pills and powders. For one thing, realgar is insoluble in water; for another, heating realgar in decoction is unsafe. Pills and powders containing realgar should also not be stored for long in sunlight or at high temperatures, to avoid deterioration and poisoning upon ingestion.

TCM has a long history of using realgar; it is recorded in the earliest materia medica work, the Shennong Bencao Jing. The Shennong Bencao Jing holds that realgar is "bitter, balanced and cold; it governs cold and heat, scrofulous ulcers, malignant sores, carbuncles and hemorrhoids, dead muscle; it kills demonic entities and evil ghosts and pathogenic qi, and the toxins of a hundred insects." The ancients believed realgar could ward off evil: if a person carried the scent of realgar, snakes, insects, ghosts, and spirits would not approach. Hence in ancient times, during the summer and autumn when snakes and insects were active, there was a tradition of drinking realgar wine and wearing realgar sachets.

TCM holds that realgar is pungent in taste, warm in nature, and toxic, entering the Liver and Large Intestine meridians. It has the effects of detoxifying and killing parasites, drying dampness and resolving phlegm, and stopping malaria. It is mainly used for carbuncles, ding abscesses, scabies and tinea, erysipelas, damp sores, hemorrhoids, snake and insect bites, throat wind and throat obstruction, epilepsy, malaria, glomus and concretions, nasal polyps, and cough and asthma.

From ancient times to the present, people have known realgar to be toxic, so its dosage is used with extreme caution. In pills and powders, each dose is only 0.1–0.15 g. Materia medica works through the ages all state that realgar is best used externally; internal use must be cautious and should "stop as soon as the disease is addressed" (zhong bing ji zhi): once the condition improves, realgar should be temporarily or completely discontinued. The Bencao Jing Shu states that realgar "is hot and toxic; externally its merits are readily seen, while internal use is unavoidably harmful. Whenever it is taken, stop as soon as the disease is addressed; do not finish the full course."

Ancient alchemists often used violent poisons like realgar and cinnabar to concoct elixirs, claiming that taking them would grant immortality; these elixirs poisoned many people to death, and Emperor Yongzheng of the Qing dynasty is believed to have died from elixir poisoning. Li Shizhen wrote in the Bencao Gangmu: "Realgar is a key herb for treating sores and killing toxins. Because it enters the qi portion of the Liver meridian, it has remarkable efficacy for liver wind, liver qi, convulsive epilepsy, phlegm-salivation, headache and dizziness, summer-heat malaria, diarrhea and dysentery, and glomus and concretions. It can also transform blood into water. But the alchemists refined it for ingestion and made marvelous claims; many have been poisoned by it."

Realgar is an important anti-leukemia and anticancer drug, widely used in the treatment of lung cancer, liver cancer, gastric cancer, leukemia, ovarian cancer, nasopharyngeal cancer, cutaneous squamous cell carcinoma, and esophageal cancer, among many malignancies.

Realgar is also an effective single herb for herpes zoster: 50 g of realgar added to 100 ml of 75% medical alcohol to make a suspension, applied to the affected area, has a cure rate exceeding 90%. Realgar can also treat vaginal trichomoniasis and tinea manuum. In ancient times there was a formula called Sishen San (Four Spirits Powder) for vitiligo and purpura: equal parts of realgar, orpiment, sulfur, and alum ground to a fine powder, mixed with ginger juice and applied to the affected area; records say four or five applications sufficed to cure.

Realgar is a specific drug for leukemia. Realgar has a dual effect on acute promyelocytic leukemia (APL) NB4 cells, simultaneously inducing apoptosis and promoting partial differentiation. Realgar can reduce telomerase activity in cancer cells and induce apoptosis in the chronic myeloid leukemia cell line K562. After treatment with realgar, NB4, HL-60, and K562 cells show characteristic morphological apoptotic changes and degradation of intracellular fusion proteins. Realgar can also induce apoptosis in the all-trans retinoic acid-resistant APL cell line MR2. Realgar induces apoptosis in the B-lymphoma cell line Raji and the T-lymphoblastic leukemia line CEM; in vitro tests show it can induce apoptosis in multiple myeloma cells. Realgar also has clear inhibitory effects on drug-resistant breast cancer and liver cancer.

Ancient physicians treated stubborn cough and asthma (mostly caused by lung cancer) by having patients inhale realgar smoke; this treatment actually used arsenic (arsenic trioxide, As2O3) to treat lung cancer, because realgar oxidizes into arsenic trioxide during fumigation. I have encountered this method in practice: I once knew a lung cancer patient who used arsenic smoke inhalation on his own and survived over five years without abnormality. I also saw an old TCM physician in Pingdingshan, Henan, use an "anticancer cigarette" containing arsenic to treat cancer; this inhalation method suits patients with lung cancer and nasopharyngeal cancer. But safety is hard to control; patients must pay close attention to dosage, must not be impatient, and should use it for a few days then stop for a few days to ensure safety.

Realgar and dried toad, in a 1:2 ratio, are made into a powder, mixed with water into a paste, and applied externally to the painful area caused by liver cancer, fixed with gauze and adhesive tape, and changed every 6–8 hours; this can treat cancer pain caused by liver cancer. Pain usually gradually eases within 15 minutes after application, and in some patients disappears completely; the effect lasts 12–24 hours. This external cancer-pain method is unsuitable for patients with broken skin or ulcers, or for those prone to skin allergy.