2019 \ ……. \ …….
2
Vitamins in treatment
of osteosarcoma cell
NAME: TAMIEM ELZWAY
STUDENT NUMBER: 1829
2ND YEAR BASIC MEDICAL SCIENCES
SUPERVISED BY: AISHA ALFAYTORY
ARTICLE NAME: TAKATSUNE SHIMIZU AND MUHAMMAD KHAN
Abstract
An important role of tow fat‑soluble vitamins serves important roles in bone
metabolism, where The present study aimed to identify the antitumor effects of
Vitamin k and D in osteosarcoma.
Vitamin K4 inhibits the proliferation and induces apoptosis of U2OS osteosarcoma
cells via mitochondrial dysfunction, VK4 arrested the cells in S phase and induced
apoptosis, Where Calcitriol inhibited cell proliferation in AXT cells by blocking cell cycle
progression by inducing endoplasmic reticulum ER stress, which was potentially
responsible for downregulation of cyclin D1, activation of p38 MAPK.
Both vitamins induce increased production of reactive oxygen species in order to
destroy osteosarcoma cell in U2OS osteosarcoma and AXT cell.
introduction
Osteosarcoma is the most common bone malignancy diagnosed in children and
young adults characterized by formation of immature bone recently treatment of OS
the combination of surgery and chemotherapy has improved the prognosis, more
than 30% of patients do not survive over the long term, and the outcomes have not
changed largely over the past 20 years, therefore novel therapeutic options are
urgently required.
otherwise, a recent study showed it can be treated by one of the following vitamins:
Vitamin K (VK) is a group of fat‑soluble vitamins that serve important roles in blood
coagulation and bone metabolism, VK exists as natural and synthetic forms.
VK1 (phylloquinone) and VK2 (menaquinone) are natural vitamins, VK3 and VK4
(menadiones) are synthetic derivatives of VK1 and VK2 (14). In recent years, an
increasing number of studies have demonstrated that VK 4 inhibits the growth and
induces apoptosis in multiple cancer cell types VK4‑induced apoptosis in these cells
remain largely unknown.
the aim of the present study was to investigate whether VK4 exerts anticancer
effects in osteosarcoma cells and to identify the potential molecular mechanisms
involved in the U2OS cell line (human bone osteosarcoma epithelium cell). (1)
Calcitriol (the active form of vitamin D), [1,25(OH)2D3 the most biologically active
hormonal form of vitamin D, is synthesized from 25(OH)D3 in the kidneys by the
cytochrome P450 enzyme.
Calcitriol regulates the balance of serum calcium and phosphate levels, which is
critical for bone mineralization Accordingly, calcitriol has been used to treat bone
diseases such as osteoporosis, rickets, and osteomalacia.
Previous investigations revealed that vitamin D, including calcitriol, alone or in
combination with other agents, exerts antineoplastic effects in osteosarcoma,
However, we examined the effects of calcitriol on osteosarcoma cells in vitro and in
vivo using our syngeneic mouse model called AXT cell. (2)
DISCUSSION
Vitamin K4 is a synthetic hydrophilic menadione compound, which is used clinically as
a treatment for hemostasis, Apoptosis and cell cycle arrest are the two major causes
of cell growth inhibition in cancer cells.
In the present study, VK4 arrested the cell cycle of U2OS osteosarcoma cells at S phase
and induced apoptosis in cells in a dose-dependent manner.
Apoptosis a form of programmed cell death is a highly controlled and evolutionarily
conserved process characterized by cell shrinkage, membrane blebbing, loss of plasma
membrane integrity, DNA fragmentation and cleavage of caspase3Consistent with
these features of apoptosis, VK4. treated U2OS cells exhibited cell shrinkage and
cleavage of caspase 3.
Apoptosis can be divided into the following three major categories:
First by the Mitochondrial caspase-dependent apoptosis or intrinsic apoptosis
Second by extrinsic apoptosis and third by caspase-independent apoptosis.
The VK4 increased ROS generation by endoplasmic reticulum stress with ROS may lead
to extensive oxidative damage, including:
mitochondrial damage, lipid peroxidation and DNA damage (apoptosis). (1)
Otherwise Previous studies of various malignancies showed that calcitriol exerts its
anti-tumor effect by directly inducing cell death, including apoptosis, or by
modulating the tumor environment in vivo in mouse cell (AXT cell)
the anti-proliferative effect in AXT cells by calcitriol was mainly attributable to
induction of cell cycle arrest Despite the growth inhibition.
Calcitriol induced ER stress in AXT cells Endoplasmic reticulum stress has not been
extensively characterized as a mechanistic cause of the cytotoxicity of calcitriol
although a recent study described this rapid downregulation of cyclin D1 at the
protein level and inhibition of the G1-to-S transition. In addition, The production of
intracellular reactive oxygen species (ROS) was significantly elevated with induce
activation of p38 MAPK in AXT cell.
Endoplasmic reticulum stress can exert opposing effects on malignant cells, either
inhibition tumor growth or inducing cell death.
Calcitriol also exerted an anti-tumor effect but it has also slide affect the drug’s
toxicity reflected by body weight loss and hypercalcemia is a problem that cannot be
ignored in a clinical context. (2)
conclusion
VK4 and calcitriol both induce inhibits the growth and induces apoptosis of U2OS and AXT cell
osteosarcoma cells Apoptosis was associated with ROS generation by endoplasmic reticulum
stress, MMP dissipation, modulation of Bcl‑2 family protein expression and activation of
caspase‑3 and downregulation of cyclin D. (1) (2)
In addition, VK4 suppressed the migration of U2OS cells in vitro. (1)
Where calcitriol suppressed the osteosarcoma (AXT cell) in vivo. (2)
References
Shimizu, T., Kamel, W., Yamaguchi-Iwai, S., Fukuchi, Y., Muto, A. and Saya, H.
(2019). Calcitriol exerts an anti-tumor effect in osteosarcoma by inducing the
.endoplasmic reticulum stress response
2. Di, W., Khan, M., Gao, Y., Cui, J., Wang, D., Qu, M., Feng, L., Maryam, A. and Gao,
H. (2019). Vitamin K4 inhibits the proliferation and induces apoptosis of U2OS
.osteosarcoma cells via mitochondrial dysfunction
,