1. Field
One or more embodiments relate to a composition for preventing or treating skin cancer, and more particularly, to pharmaceutical composition for preventing or treating skin cancer, the composition comprising a Panax spp. plant extract containing 90% or more of Rg3, Rk1, and Rg5 with respect to a weight of ginsenoside Rb1, Rc, Rb2, Rd, Rg3, Rk1, and Rg5 obtainable by irradiating microwaves to a Panax spp. plant or an extract thereof as an active ingredient and method of method of preventing or treating skin cancer in a subject using the composition.
2. Description of the Related Art
Skin is a tissue that serves as a barrier at the outermost part of the body to protect various organs and muscles in the body from the external environment. The skin is the heaviest organ in the body, and its functions include heat-resistance and body temperature regulation. The skin serves as an organ that senses various stimuli such as temperature, pressure, and pain and involves in storage of lipid and water and synthesis of vitamin D. The term “skin cancer” refers to all types of malignant tumor that is formed in skin tissue. The skin cancer is mainly caused by environmental external stimuli, such as ultraviolet (UV) light, or genetic factors. Family history in certain genes, such as a KIT gene, has been known as having an influence on skin cancer. However, a factor known to have the most influence on skin cancer is external stimuli, such as UV light, occurrence of skin cancer has increased along with frequent outdoor activities as western lifestyle has been introduced, sun tanning and increased use of tanning devices, and increased amount of transmitted UV light due to a weakened ozone layer. When exposed to a large amount of UV light, thymidine dimmers may be formed or double-strand breakage may occur in DNAs in cells. When the damaged DNAs are not repaired properly, proto-oncogenes turn into oncogenes, and tumor suppressor genes may lose their functions. In this case, cell division regulation mechanisms in skin cells may not normally operate, which results in unlimited amplification, and thus normal cells are mutated into tumor cells. The cancerous tissue drags blood vessels nearby through hormone secretion to be supplied with nutrition, and, at the same time, the cancerous cells themselves are metastasized to other parts of the body through lymph nodes and blood vessels. A case when tumor occurred in skin is classified as ‘primary’ skin cancer, and a case when tumor started out from another organ and then metastasized and settled in skin is classified as ‘metastatic’ skin cancer, but skin cancer of general definition refers to primary skin cancer. Although skin cancer is one of the most common cancers in Caucasians, studies on skin cancer has not been actively conducted since it generally has a low fatality compared to those of cancers that occur in internal organs. However, skin cancer occupies 2.0% of all cancers occurred in the Republic of Korea based according to the statistics in 2012. Skin cancer can be diagnosed by using diagnostic devices such as computed tomography (CT) or ultrasound waves, as well as through observation with the naked eye and biopsy, but in many cases, the delay in initial discovery by taking the symptoms lightly may increase complete recovery rate and survival rate. The skin cancer may be classified into squamous cell carcinoma, basal cell carcinoma, or melanoma depending on which cells constituting skin tissue the skin cancer is derived from. Squamous cell carcinoma, which is a malignant tumor derived from epidermal keratinocytes, and basal cell carcinoma, which arises when the basal cell layer, the lowest layer of epidermis, or hair follicle cells turn into malignant tumor cells, are common skin cancers among those diagnosed in the Republic of Korea but have relatively low fatality. On the other hand, malignant melanoma is a cancer that originates from melanin cells, which determine color of skin, and has the highest degree of malignancy and easily penetrate and metastasize. Thus, malignant melanoma is a dangerous cancer as humans have a low survival rate with malignant melanoma.
Panax ginseng is a perennial plant belonging to the Panax species, Araliaceae family. Examples of Panax species plants having a similar efficacy to Panax ginseng include Panax quinquefolia, Panax notoginseng, Panax japonica, Panax Trifolia, Panax pseudoginseng, Panax vietnamensis, and the like. These Panax species plants contain dammarane-based saponin in common with 1 to 4 saccharide(s) combined to a dammarane backbone, unlike other plants. In particular, saponins contained at high concentration in ginseng include ginsenosides Rb1, Rb2, Rc, Rd, Rg1, and Re. These saponins have a variety of pharmaceutical effects that greatly differ in types and intensities depending on the structures thereof.

The dammarane-based saponin of the Panax species plants has protopanaxadiol (PPD) or protopanaxatriol (PPT) as a core nucleus, and may be classified as illustrated in Formula 1. A dammarane-based saponin may be classified according to R1, R2, and R3 in Formula 1 as below
TABLE 1GroupGinsenosideR1R2R3ProtopanaxadiolRa1-Glc-Glc—H-Glc-Ara(pyr)-Xyl(PPD)Ra2-Glc-Glc—H-Glc-Ara(fur)-XylRa3-Glc-Glc—H-Glc-Glc-XylRb1-Glc-Glc—H-Glc-GlcRb2-Glc-Glc—H-Glc-Ara(pyr)Rb3-Glc-Glc—H-Glc-XylRc-Glc-Glc—H-Glc-Ara(fur)Rd-Glc-Glc—H-GlcRg3(20-R,S)-Glc-Glc—H—HRh2(20-R,S)-Glc—H—HRs1-Glc-Glc-Ac—H-Glc-Ara(pyr)Rs2-Glc-Glc-Ac—H-Glc-Ara(fur)Rs3-Glc-Glc-Ac—H—Hmalonyl-Rb1-Glc-Glc-—H-Glc-Glcmalonylmalonyl-Rc-Glc-Glc-—H-Glc-Ara(fur)malonylmalonyl-Rd-Glc-Glc-—H-Glcmalonylpseudoginsenoside-Glc—H-GlcF2notoginsenoside Fe-Glc—H-Glc-Ara(fur)ProtopanaxatriolRe—H-OGlc--Glc(PPT)RhaFf—H-OGlc-—HGlcRg1—H-OGlc-GlcRg2(20-R,S)—H-OGlc-—HRhaRh1(20-R,S)—H-OGlc—Hnotoginsenoside—H-OGlc--GlcR1Xylnotoginsenoside—H-OGlc-—HR2Xylpseudoginsenoside—H—OH-GlcF1pseudoginsenoside-Glc-GlcAc—OH-Glc-GlcF8pseudoginsenoside—H—OH-Glc-Ara(pyr)F3Rh4—H-OGlc-methyl
Rg5 and Rk1 are compounds that may be each respectively represented by Formulae 2 and 3, wherein R1 is -Glc-Glc, and R2 is —H.

Protopanaxadiol-type ginsenosides Rb1 and Rb2 may produce 20(S)-Rg3 and 20(R)-Rg3 when -Glc-Glc or -Glc-Ara(pyr) is dissociated at position 20. Also, Rg5 and Rk1 may be produced when H2O is dissociated at position 20 of 20(S)-Rg3 and 20(R)-Rg3. Ginsenoside Rg5 is known for its antioxidative effects, promotion of brain function and cognitive function, blood vessel expansion effects, inhibitory effects on platelet aggregation, improving effects on dermatitis and/or psoriasis, and anti-inflammatory effects. Ginsenoside Rk1 is known for its blood vessels expansion effects, inhibitory effects on platelet aggregation, and improving effects on brain function and cognitive function such as memory and learning ability, prevention of dementia through the activation of brain cells, anti-aging and anti-cancer and cell regeneration. Ginsenoside Rk1 is known for its blood vessels expansion effects, inhibitory effects on platelet aggregation, and improving effects on brain function and cognitive function. Studies on a ginseng extract having a sufficiently increased content ratio of ginsenoside Rg5 and Rk1 is needed. Also, since ginsenoside Rg5 and Rk1 may be derived from ginsenoside Rg3, a ratio of ginsenoside (Rg5+Rk1)/(Rg3) is important in defining a content increase of Rg5 and Rk1.
The related conventional art has not disclosed whether a composition including a Panax spp. plant extract containing 90% or more of Rg3, Rk1, and Rg5 with respect to a weight of ginsenoside Rb1, Rc, Rb2, Rd, Rg3, Rk1, and Rg5 has prevention or treatment effects on skin cancer or not.